Our objective is to develop and apply suitable methods of cell cycle analysis with which the growth kinetics of cancer and normal cells from man and experimental animals can be understood in the context of cancer therapy with drugs and radiation. We are especially interested in flow cytometric methods of kinetic analysis because they offer the promise of powerful, sensitive, rapid, and practical approaches to kinetic analysis under steady state and in the midst of therapy. We are continuing kinetic technique development in vitro using KHT tumor cells and dual Chinese hamster ovary (diploid and tetraploid cultures) system. Emphasis is currently on the cell cycle kinetic response of these cells to multiple doses of the cell cycle phase specific agent cytosine arabinoside (Ara-c). We are continuing application of our techniques to study of the response of KHT cells in vivo to multiple doses of Ara-c. We are also developing high pressure liquid chromatographic and radioimmune assay techniques for measurement of picogram levels of drugs and drug metabolites during therapy for correlation with the cell cycle kinetic effects. Extensive computer programs are being developed for the analysis of our cell cycle and pharmacokinetic data.